Abstract

Introduction: Osteoporosis is characterized by a decrease in bone mass and density with enlarged trabecular space resulting in porosity and bone fragility. It has been described in as many as 70 to 80% of adults with thalassemia (Thal) and sickle cell disease (SCD). Though assessment by DXA scan is now part of routine clinical practice, bone quality has been poorly characterized, particularly in SCD. Trabecular bone score (TBS) is a new textural analysis of lumbar spine DXA scans that reflects bone microarchitecture, shown to be highly predictive of fracture in adults. The objectives of this study were 1) to determine the prevalence of poor bone quality as assessed by TBS in patients with Thal and SCD, compared to healthy individuals and 2) to assess the relationship between bone quality and clinical predictors (age, transfusion status, liver iron concentration, diet, BMI, endocrinopathies).

Methods: A retrospective chart review was conducted in patients > 10 years and > 40 Kg with Thal or SCD who had a spine bone mineral density (BMD) scan performed in the previous 5 years. Patients had on average 1.7±0.9 spine scans during the collection period (range 1-5); all scans were reanalyzed using the TBS software (Insight, MediMaps v2.2, France). Optimal bone quality was defined as TBS >1.35; subnormal TBS= 1.34-1.20; abnormal <1.20. Liver iron concentration (LIC) was assessed by SQUID. Data from healthy controls without Thal or SCD were collected from previously completed research studies. Statistical analysis was performed using STATA, v. 9.0 (College Station, TX). This study was approved by the Institutional Review Board at UCSF Benioff Children's Hospital Oakland.

Results: Data from 251 patients were abstracted which included, 162 females, 173 adults; 81 Thal, 102 SCD, and 68 healthy controls. Thal patients were older than SCD or controls (29.7 vs. 23.8, 25.8 years, p<0.05) and had lower LIC (2303 vs. 3014 µg Fe/g wet wt., p=0.004) but higher incidence of hypogonadism (31% vs. 1%, p<0.001). No differences were observed in vitamin D status, fracture history or family history of osteoporosis. On average, Thal patients had greater deficits in spine BMD Z-score (-2.1±1.2, Mean±SD), as compared to SCD (-1.0±1.5) and controls (-0.1±0.8), as well as a higher prevalence of abnormal bone quality by TBS (29.7%) vs. 12.2% in SCD, 4.6% in control, (p<0.001). TBS was positively correlated with BMD (r=0.7, p<0.001) and negatively correlated with age (r=-0.28, p<0.001). After controlling for age, BMI, hypogonadism and diagnosis, LIC was negatively associated with bone quality (r=0.30, p=0.001).

Conclusions: These data support the relationship between reduced bone mass and bone quality in adult and adolescent patients with hemoglobinopathies. Older patients with low bone mass appear to be at particular risk for abnormal bone quality. TBS may be a valuable clinical tool in the assessment of true fracture risk in this group of patients with extremely low bone mineral density. However, future research is needed to develop models that include BMD and TBS for prediction of absolute fracture risk and need for treatment of low bone mass in patients with hemoglobinopathies.